Nitrous Oxide

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The use of Nitrous Oxide

  • I don't care what's published. I will keep using N2O

    Votes: 7 13.0%
  • I will wait for Enigma 2. Until then business as usual

    Votes: 14 25.9%
  • I plan on curtailing the use of N2O. Short cases or wake-up only

    Votes: 16 29.6%
  • I was never a N2O fan. Now I have good evidence.

    Votes: 17 31.5%

  • Total voters
    54

BLADEMDA

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The Enigma 1 Study is another nail in the coffin for Nitrous lovers out there.
Midlevel providers and others who don't read the literature need to be aware of the changing tide as it regards Nitrous Oxide. Perhaps the upcoming Enigma 2 study will provide the final blow to the use of Nitrous Oxide for adults in cases over 2-2.5 hours.

http://www.anesthesia-analgesia.org/content/early/2010/09/22/ANE.0b013e3181f7e2c4.abstract

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The Enigma 1 Study is another nail in the coffin for Nitrous lovers out there.
Midlevel providers and others who don't read the literature need to be aware of the changing tide as it regards Nitrous Oxide. Perhaps the upcoming Enigma 2 study will provide the final blow to the use of Nitrous Oxide for adults in cases over 2-2.5 hours.

http://www.anesthesia-analgesia.org/content/early/2010/09/22/ANE.0b013e3181f7e2c4.abstract

too many questions in this study left unanswered, notably:

why such a high death rate; 20% 3-year mortality seems way too high.

losing greater than 10% of your study to follow up for "insufficient research staff" is shameful

also, id like to know the delta in homocysteine values among the patients who suffered an MI between the two groups. overall its not the best study, IMHO

so, ill continue to avoid N2O in certain patients (older patients at increased risk of CAD/MI) just like I always would.
 
too many questions in this study left unanswered, notably:

why such a high death rate; 20% 3-year mortality seems way too high.

losing greater than 10% of your study to follow up for "insufficient research staff" is shameful

also, id like to know the delta in homocysteine values among the patients who suffered an MI between the two groups. overall its not the best study, IMHO

so, ill continue to avoid N2O in certain patients (older patients at increased risk of CAD/MI) just like I always would.

Yes. The editorial in Feb 2011 Anesthesia and Analgesia discussed all those points. Enigma 2 should provide better clarity.
 
too many questions in this study left unanswered, notably:

why such a high death rate; 20% 3-year mortality seems way too high.

losing greater than 10% of your study to follow up for "insufficient research staff" is shameful

also, id like to know the delta in homocysteine values among the patients who suffered an MI between the two groups. overall its not the best study, IMHO

so, ill continue to avoid N2O in certain patients (older patients at increased risk of CAD/MI) just like I always would.

Did you vote for choice 2 in the poll? The evidence to this point does seem to strongly suggest avoidance of N2O in high risk patients undergoing a long anesthetic is probably a wise choice.
 
No change needed: "Nitrous oxide did not significantly increase the risk of death [hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82)]."
 
No change needed: "Nitrous oxide did not significantly increase the risk of death [hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82)]."

So having an MI is a benign thing? What about loss of Cardiac function and diminished quality of life?
 
Nausea or vomiting after surgery is rated by patients as
one of the most undesirable postoperative complications.
16 Our study found a marked reduction in the rate
of severe nausea or vomiting in the first 24 h after
surgery in the nitrous oxide–free group. Although this is
consistent with the findings from one large trial (but our
effect size is larger, perhaps due to longer duration of
surgery)15 and a meta-analysis of small trials,14 our findings
have greater clinical applicability, because minor or
transient nausea or vomiting was excluded and so only
genuinely distressing severe nausea or vomiting was included.
16 The incidence of severe nausea or vomiting
within 24 h of surgery in our study was reduced from
23% in the nitrous oxide group to 10% in the nitrous
oxide–free group, giving a number needed to treat of 8.
The simple intervention of removing nitrous oxide from
the anesthetic regimen should therefore have a substantial
impact on patient comfort after surgery.16 Indeed,
we demonstrated a subsequent improved quality of recovery
in patients in whom nitrous oxide was omitted.


http://www.ncbi.nlm.nih.gov/pubmed/17667565
 
i guess ill peruse the editorial then, i plan on continuing to avoid in high risk populations.

Yes. The editorial explains in detail why we need Enigma 2. Your approach to N2O based on current available evidence is sound. I have chosen choice 3 from the poll above but am prepared to alter my practice based on the outcome of Enigma 2.
 
I tell all my residents that in the next 10-15 yrs nitrous will be, at best, an option-only thing on anesth machines
 
keep in mind that ENIGMA patients were randomized to 70%N2O and clearly they were a sicker population than a typical cross section, based on overall mortality data. I havent run someone on 70% except for like 5 minutes at the end of a case waiting for med student closure. clearly a better study would be a more practical one with volatile/O2 vs volatile/N2O/O2 since that is what most of us do. im not current on this topic enough to know if thats been done, but i plan on following it up.
 
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I can't remember the last time I used nitrous for anything other than a pediatric mask induction (turned off after induction), a GA c-section (less volatile = less uterine atony), or when I relieve somebody and take over their case :)().
 
I can't remember the last time I used nitrous for anything other than a pediatric mask induction (turned off after induction), a GA c-section (less volatile = less uterine atony), or when I relieve somebody and take over their case :)().

you know....that's been studied....no faster than sevo alone.
 
Its a BS study. You cannot compare 30% oxygen vs 80% oxygen. They should have had standardized the FiO2.
 
The sevo group got 80% oxygen, while the nitrous group got 30% oxygen. This is a confounding variable and makes any conclusions about the study questionable.
 
you know....that's been studied....no faster than sevo alone.

I don't use nitrous for pediatric mask inductions because I think it's faster.

I use it (in selected cases) because I think some older kids have a less scary experience if they get some non-stinky gas to relax them first.
 
The sevo group got 80% oxygen, while the nitrous group got 30% oxygen. This is a confounding variable and makes any conclusions about the study questionable.

so you're saying that FIO2 levels will change your rate of induction?

and confound end points like ....incidence of hypoxia and desaturation?
 
I don't use nitrous for pediatric mask inductions because I think it's faster.

I use it (in selected cases) because I think some older kids have a less scary experience if they get some non-stinky gas to relax them first.

ok
 
The difference in FiO2 between the group is so large that maybe it did affect the outcomes studied. Maybe due to hypoxia/relative hypoxia in the nitrous group. Maybe it didn't, but you cannot really say unless the study is done with equal FiO2 in both groups....
 
At a quick glance, it seems ENIGMA looks at ASA III/IV patients and had Nitrous run for 2+ hrs duration. What do people think about Nitrous at end of a case in ASA I/II pts, maybe the last 30min-1hr for faster wakeup and analgesic effect (avoid giving additional narcotic at the end, leading to faster emergence)? Someone mentioned earlier that Sevo is just as fast off, I can't seem to find any data on that...doesn't seem to be true in my experience. Sevo always seems to lag around an Et 0.2-0.4 while it is being redistributed out. People talk about Nitrous and PONV, but from what I can gather, there is little to no increased risk if ran for less than an hour. (source below)

http://www.ncbi.nlm.nih.gov/pubmed/24401771
 
Enigma 2 is out. Nitrous has not been linked to increased mortality. That said, I use Nitrous sparingly in ASA 4 cases and prefer to use it at the end of the case for speedy wake-ups.
 
Interpretation
Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown.


http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60893-X/abstract
 
I have made a U-turn on nitrous. After not using it almost ever after Enigma 1, I find myself using it quite a bit more often now.

Where I use it quite a bit nowadays is actually for MAC cases if the usual deep propofol sedation is sketchy for whatever reason. In many ways it's an ideal sedative, in that it's analgesic, the hemodynamics don't budge, and they keep breathing. A whiff of propofol in the background as frosting, and they wake up clear-headed and happy. I do my "conscious sedation" TAVRs this way.

For GA I usually use a full MAC of des, since it goes away about as quick as nitrous anyway. Wouldn't hesitate anymore to go to a half MAC of nitrous in an elderly patient that could take the full MAC of volatile, whereas I would have hesitated before ENIGMA II came out.

If I take over a partner's case and they're running sevo I'll often land the patient on nitrous if it's a teaching room and a resident is closing.
 
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Nitrous oxide is a very useful agent , it does not have to be part of every anesthetic but it has some elegant indications.
This thread is a great example of why we should always take new literature for what it's worth, and remember that about 80% of the published studies are garbage.
 
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I have made a U-turn on nitrous. After not using it almost ever after Enigma 1, I find myself using it quite a bit more often now.

Where I use it quite a bit nowadays is actually for MAC cases if the usual deep propofol sedation is sketchy for whatever reason. In many ways it's an ideal sedative, in that it's analgesic, the hemodynamics don't budge, and they keep breathing. A whiff of propofol in the background as frosting, and they wake up clear-headed and happy. I do my "conscious sedation" TAVRs this way.

For GA I usually use a full MAC of des, since it goes away about as quick as nitrous anyway. Wouldn't hesitate anymore to go to a half MAC of nitrous in an elderly patient that could take the full MAC of volatile, whereas I would have hesitated before ENIGMA II came out.

If I take over a partner's case and they're running sevo I'll often land the patient on nitrous if it's a teaching room and a resident is closing.
For Mac with nitrous do you deliver via nasal canula? Or do you just strap on a mask?
 
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At a quick glance, it seems ENIGMA looks at ASA III/IV patients and had Nitrous run for 2+ hrs duration. What do people think about Nitrous at end of a case in ASA I/II pts, maybe the last 30min-1hr for faster wakeup and analgesic effect (avoid giving additional narcotic at the end, leading to faster emergence)? Someone mentioned earlier that Sevo is just as fast off, I can't seem to find any data on that...doesn't seem to be true in my experience. Sevo always seems to lag around an Et 0.2-0.4 while it is being redistributed out. People talk about Nitrous and PONV, but from what I can gather, there is little to no increased risk if ran for less than an hour. (source below)

http://www.ncbi.nlm.nih.gov/pubmed/24401771
I work with outpatients. I run 50% nitrous on almost everything and everybody (even 3-4 hour plastics cases, we don't have des). I also don't wake them up on nitrous, but on 100% O2 (I turn off sevo last). That adds a degree of safety (patient preoxygenated, minimal diffusion hypoxia if any in the PACU), and makes my patients less groggy at wakeup (in my very subjective experience). I also seldom run sevo at more than 1%.

I tend to be very conservative with opiates. IMO they are the main culprit for nausea, not nitrous. I try to limit the dose to less than 100 mcg of fentanyl, and very little, if any, dilaudid (for certain procedures only).

The people who will puke from nitrous are the people who will puke from almost anything (sevo, 25 mcg of fentanyl, you name it), generally less than 1% of the population. Nitrous is theoretically more emetic when the patient has motion sickness, because its effect on any air trapped in the middle ear.

So don't be afraid of nitrous, and don't think it's a CRNA "tool" which shows incompetence (as some of my attendings used to tell me in residency - people who haven't done a solo case in years, of course). It's a cheap and great tool to have in your arsenal.

Also, don't forget that nitrous has been self-administered for labor in Europe for decades, with no puking.
 
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This thread is a great example of why we should always take new literature for what it's worth, and remember that about 80% of the published studies are garbage.
This should be the motto of "evidence-based" medicine, except that I believe that the number is much higher. To paraphrase somebody's earlier post: Blade would be able to "prove" anything he wants to, by finding a bunch of studies that support his view.

This is why inexperienced doctors should never guide themselves by studies (many of which will be proven wrong by similarly worthless ones), but by what they glean from truly experienced senior people. Nothing beats decades of experience. There is a reason we used to have 1:1 apprenticeships, not 2:1 "residencies". E.g. droperidol has that crazy black box warning, which made it virtually disappear, while being one of the best last-resort antiemetics, even in a small dose (0.625 mg IV).

And this is why textbooks should be written by a very small group of true practical experts, not a sea of ivory tower study processors with limited practical experience. Why Marik's or Marino's ICU books are so great, and why Clinical Anesthesiology will probably teach you more and faster than Clinical Anesthesia. Etc. ;)
 
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I have grown to love nitrous, given that our institution uses iso for nearly all GA cases (most rooms don't even have sevo or des vaporizers in the machine's storage slots). Typically run 50% N2O for the case to spare iso, then turn off iso and convert to 60-70% when they start closing, then up to 100% O2 when drapes come down. Patient is usually just starting to wake up as we transfer them to the bed. I have yet to use it for a MAC case, but it's on my list to do.
 
Yeah, you can almost think of nitrous as inhaled ultra-short-acting ketamine when it comes to MAC cases, given the NMDA antagonism, respiratory effects, etc.
 
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Unfortunate that the analgesic effect of N2O is abolished when combined with a potent volatile. There's a good paper out there outlining the pharmacology of this phenomenon.
 
Unfortunate that the analgesic effect of N2O is abolished when combined with a potent volatile. There's a good paper out there outlining the pharmacology of this phenomenon.

I don't think you are correct here slim. You have one rat study and I have another disproving it.

Here is your rat study:

http://bja.oxfordjournals.org/content/76/5/702.full.pdf html

Here is my rat study:
http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1918268



Nitrous Oxide and Its Synergistic Interaction with Isoflurane

35 a high dose of naloxone showed no effect upon the suppressed release. The synergistic interaction observed here parallels the behavioral literature. Although some reports refer to the fact that volatiles such as halothane and isoflurane may antagonize nitrous oxide analgesia,36 we saw no evidence of such a negative effect on substance P release of c-Fos activation here, and nitrous oxide is MAC-sparing, when used with volatile anesthetics.37–3
 
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Ha, I knew I could count on you Blade to dig up the lit. I don't know, I think my rat study which looks at tail-flick (a well accepted/established model for pain tolerance and analgesic effects) trumps your rat study which looks only neurotransmitter effects in harvested spinal cord samples s/p anesthesia.

Clinically/anecdotally I just haven't felt that the addition of N2O to a volatile anesthetic has had any analgesic effect (while maintaining equal MAC values). Try going from 1 MAC of sevo to 1/2 MAC sevo and 1/2 MAC N2O. I don't think you will see any relevant analgesia. I played around with this for a while as a resident after coming across these studies.
 
Neither of those is the paper I was thinking of though which outlines the pharmacological interactions between the agents. I'll see if I can summon my inner Blade and dig that one up.
 
Neither of those is the paper I was thinking of though which outlines the pharmacological interactions between the agents. I'll see if I can summon my inner Blade and dig that one up.


Fine. But, I wanted the residents to see there is Controversy in this area; regardless, the subject makes a great written board question or ITE.
 
I don't use it a lot because i use fresh gas flow rates of around 0.35l/min
I like to use it for putting iv in awake bigger children instead of having to do an inhalation induction.
 
Anesthesia & Analgesia:
August 2000 - Volume 91 - Issue 2 - pp 462-466
doi: 10.1213/00000539-200008000-00044
General Articles
Inhaled Anesthetics Have Hyperalgesic Effects at 0.1 Minimum Alveolar Anesthetic Concentration
Zhang, Yi MD; Eger, Edmond I II MD; Dutton, Robert C. MD; Sonner, James M. MD



icon-minus.gif

Abstract

We investigated the hyperalgesic (antianalgesic) effect of the inhaled anesthetics isoflurane, halothane, nitrous oxide, and diethyl ether, or the nonimmobilizer 1,2-dichlorohexafluorocyclobutane at subanesthetic partial pressures (or, for the nonimmobilizer, subanesthetic partial pressures predicted from lipid solubility) in rats. Hyperalgesia was assessed as a decrease in the time to withdrawal of a rat hind paw exposed to heat. All four anesthetics, including nitrous oxide and diethyl ether, produced hyperalgesia at low partial pressures, with a maximal effect at 0.1 minimum alveolar anesthetic concentration (MAC) required to prevent response to movement in 50% of animals, and analgesia (an increased time to withdrawal of the hind paw) at 0.4 to 0.8 MAC. The nonimmobilizer had neither analgesic nor hyperalgesia effects. We propose that inhaled anesthetics with a higher MAC-Awake (the MAC-fraction that suppresses appropriate responsiveness to command), such as nitrous oxide and diethyl ether, can be used as analgesics because patients are conscious at higher anesthetic partial pressures, including those which have analgesic effects, whereas anesthetics with a lower MAC-Awake do not produce analgesic effects at concentrations that permit consciousness.

Implications: The inhaled anesthetics isoflurane, halothane, nitrous oxide, and diethyl ether produce antianalgesia at subanesthetic concentrations, with a maximal effect at approximately one-tenth the concentration required for anesthesia. This effect may enhance perception of pain when such small concentrations are reached during recovery from anesthesia.
 
Anesthesiology. 2010 Jun;112(6):1452-63. doi: 10.1097/ALN.0b013e3181d94e00.
Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction.
Eilers H1, Cattaruzza F, Nassini R, Materazzi S, Andre E, Chu C, Cottrell GS, Schumacher M, Geppetti P, Bunnett NW.
Author information

Abstract
BACKGROUND:
Volatile anesthetics such as isoflurane and halothane have been in clinical use for many years and represent the group of drugs most commonly used to maintain general anesthesia. However, despite their widespread use, the molecular mechanisms by which these drugs exert their effects are not completely understood. Recently, a seemingly paradoxical effect of general anesthetics has been identified: the activation of peripheral nociceptors by irritant anesthetics. This mechanism may explain the hyperalgesic actions of inhaled anesthetics and their adverse effects in the airways.

METHODS:
To test the hypothesis that irritant inhaled anesthetics activate the excitatory ion-channel transient receptor potential (TRP)-A1 and thereby contribute to hyperalgesia and irritant airway effects, we used the measurement of intracellular calcium concentration in isolated cells in culture. For our functional experiments, we used models of isolated guinea pig bronchi to measure bronchoconstriction and withdrawal threshold to mechanical stimulation with von Frey filaments in mice.

RESULTS:
Irritant inhaled anesthetics activate TRPA1 expressed in human embryonic kidney cells and in nociceptive neurons. Isoflurane induces mechanical hyperalgesia in mice by a TRPA1-dependent mechanism. Isoflurane also induces TRPA1-dependent constriction of isolated bronchi. Nonirritant anesthetics do not activate TRPA1 and fail to produce hyperalgesia and bronchial constriction.

CONCLUSIONS:
General anesthetics induce a reversible loss of consciousness and render the patient unresponsive to painful stimuli. However, they also produce excitatory effects such as airway irritation and they contribute to postoperative pain. Activation of TRPA1 may contribute to these adverse effects, a hypothesis that remains to be tested in the clinical setting.
 
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